Development of PLGA-Mannosamine Nanoparticles as Oral Protein Carriers

Abstract

Here we report the development of polymeric nanoparticles, made of poly(lactide-co-glycolide) (PLGA) chemically modified with mannosamine (MN), intended to specifically interact with the intestinal mucosa and facilitate the intestinal transport of proteins. PLGA-MN nanoparticles displayed nanometric size and a negative zeta potential, which was lower than that of the PLGA nanoparticles. This correlate well with the preferential location of the MN group on the nanoparticles surface obtained by X-ray photoelectron spectroscope (XPS). The presence of MN groups in the polymer chain led to a different surface morphology noted by SEM, an increase of the encapsulation of model proteins, and to help stabilizing the nanoparticles in simulated intestinal fluids. Furthermore, the MN modification significantly enhanced the nanoparticle's interaction with the epithelial cells in human intestinal follicle-associated epithelium cell culture model. Overall, the MN modification significantly modifies the properties of PLGA nanoparticles making them more suitable as nanocarriers for oral protein delivery.

Functionalized PEG‐b‐PAGE‐b‐PLGA triblock terpolymers as materials for nanoparticle preparation

“…The zeta potential (ζ) for the PEG‐ b ‐PLGA and PEG‐ b ‐PAGE‐ b ‐PLGA nanoparticles increases comparing to pure PLGA particles (around −60 mV) as described in literature. For example the value for the particles of PEG‐ b ‐PLGA ( 15 ) of −15 mV is in good agreement with previously published data . Introduction of PEG into PLGA polymers increases the surface charge what can be caused by the shielding effect of PEG and is additionally influenced by the particle size (distance to the surface) .…”

“…For example the value for the particles of PEG-b-PLGA (15) of 215 mV is in good agreement with previously published data. [48][49][50][51] Introduction of PEG into PLGA polymers increases the surface charge what can be caused by the shielding effect of PEG and is additionally influenced by the particle size (distance to the surface). 48,52 Scanning electron microscopy (SEM) revealed a spherical shape of the formed nanoparticles (Fig.…”

Polymer degradation and drug delivery in PLGA‐based drug–polymer applications: A review of experiments and theories

“…As a surface modification agent, PEG—a hydrophilic, flexible, and nonionic polymer—has been broadly used to protect proteins from denaturation, to maintain bioactivity of nerve growth factor, and to improve the stability and dispersion of PLGA nanoparticles in biological fluids …”

“…The biodegradation products from PLGA are lactic acid (LA) and glycolic acid (GA), which are biologically inert to the growing cells and are removed from the body by normal metabolic pathways . As a biodegradable polymer with good biocompatibility, low toxicity, relatively high miscibility with other polymers and adjuvants as well as film‐forming and capsule‐forming properties, during the last several decades, many PLGA‐based drug–polymer systems have been developed and employed for treatment of various diseases . The compositional forms of PLGA are usually identified by their monomer ratio; for instance, PLGA 75/25 indicates a copolymer whose composition is 75 wt % PLA and 25 wt % PGA (i.e., LA/GA = 75/25).…”

Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins

“…Until now, many peptides and proteins have been approved by FDA for treatments of various human diseases (Glassman and Balthasar, 2014;Lu et al, 2006). PLGA micro/nanoparticles for protein delivery have many advantages, including the enhancement of stability, prolonged circulation time and increased bioactivity in vivo, etc (Mundargi et al, 2008;Danhier et al, 2012;Alonso-Sande et al, 2013;Varshochian et al, 2013). Thus, many investigations have focused on the design and preparation of PLGA micro/ nanoparticle systems for the delivery of proteins.…”